1. Field of the Invention
This invention relates generally to laser systems, and their methods of use, that produce short and controlled pulse width trains, and more particularly to frequency doubled, cw laser systems, and their methods of use, that produce visible pulse trains of the appropriate pulselength, duty factor, and power to perform ophthalmology treatments currently being performed in the near-infrared.
2. Description of the Related Art
Laser photocoagulation (PC) is the current standard of care for the treatment of certain retinal diseases such as diabetic macular edema (DME), proliferative diabetic retinopathy (PDR), extrafoveal, juxtafoveal and some types of subfoveal retinal neovascularization (SRNV). The laser PC protocols validated by the diabetic retinopathy study (DRS), the early treatment of diabetic retinopathy study (ETDRS) and the macula photocoagulation study (MPS) all provide evidence for the beneficial use of lasers. Most of these treatments have been conducted with visible lasers (green and red lasers). All of these laser treatments are based upon obtaining a visible endpoint as the optimal tissue reaction, which becomes visible during the laser treatment. These laser pulsewidths are typically 50 to 300 milliseconds.
Current ophthalmic diode pumped solid state green lasers have pulsewidths of 10 to 60,000 milliseconds. This pulsewidth time domain is useful for the typical photothermal reactions normally requested in ocular Photocoagulation. In these applications the energy is absorbed by chromophores such as melanin or blood and conducts away from the absorbing or pigmented layers into adjacent non-absorbing and non-exposed layers—thus causing thermal damage laterally and axially into the clear layers in addition to the pigmented layers.
Microsecond short pulsed visible lasers have been demonstrated by Pankratov, “Pulsed delivery of laser energy in experimental thermal retinal photocoagulation”, Proc. SPIE, V1202, pp. 205-213, 1990, Roider et. al., “Microphotocoagulation: Selective effects of repetitive short laser pulses”, Proc. Natl. Acad. Sci, V90, pp 8643-8647, 1993, Roider et. al., “Retinal Sparing by Selective Retinal Pigment Epithelial Photocoagulation”, Arch Ophthalmol, V117, pp 1028-1034, 1999, and U.S. Pat. No. 5,302,259 by Birngruber issued in 1994. These short pulse laser treatments have demonstrated beneficial effects while minimizing choroidal damage by using a pulse train with a low duty factor to confine the thermal effects to the absorbing layer or structure. Pankratov used an acousto-optical modulator to chop a continuous wave laser with pulse trains of 0.1 to 1.0 seconds and pulsewidths from 10 to 900 microseconds. However, the longer pulsewidths with high duty cycles behaved like CW. Only the shorter pulsewidths of 10 to 50 microseconds had beneficial effects of minimal to no visible lesions. The others used Q-switched green lasers with pulsewidths of 1.7 to 5 microseconds.
The Q-switched lasers have been used for certain thermal confinement applications such as selective laser trabeculoplasty (SLT) treatment for Glaucoma and selective retinal treatment (SRT) for clinically significant diabetic macular oedema (CSMO). In this case the energy is absorbed by the chromophores in such a short time that it cannot conduct away into adjacent tissue during the laser exposure time. The chromophore is heated to damaging levels and in certain cases will boil or explode—causing local mechanical damage in addition to the thermal damage to adjacent tissues. For these treatments, thermal confinement (or lack of thermal conduction) can only be achieved for pulses shorter than the time constant of the absorbing layer, which is on the order of 1 to 30 microseconds for the retinal pigment epithelium (RPE).
Pioneering studies using Near-InfraRed (NIR) diode lasers to treat retinal diseases without using the full energy of the traditional PC laser applications have been shown by Reichel et. al., “Transpupillary Thermotherapy of occult subfoveal choroidal neovascularization in patients with age-related macular degeneration”, Ophthalmol, V106, pp 1908-1914, 1999 and by Mainster, et. al., “Transpupillary Thermotherapy: long-pulse photocoagulation, apoptosis and heat shock proteins”, Ophthalmic Surg lasers, V31, pp 359-373, 2000. These laser treatments use energies below the threshold of visible tissue reaction. Procedures using these treatments are called Minimum Intensity Photocoagulation or MIP procedures. The lost of vision associated with the traditional PC treatments is mitigated due to the lower energies being used and thus not coagulating the retina photoreceptors in the neighboring clear layers.
There are two variations of these MIP treatments—one is called Transpupillary ThermoTherapy or TTT. This performs a long, CW, sub-threshold treatment—typically for 60 seconds—as described in the above references.
The other is a CW NIR laser with short and controlled pulse widths. It generates a pulse train of short pulses (typically 100 to 10,000 microseconds) with higher power during the pulse, but significant off time between pulses (typically 5 to 25% duty factor)—allowing the energy to be confined in a small volume using the Arrhenius principle. The thermal confinement results in tissue specific photoactivation because the specific absorbing tissue, which is being heated by the pulses to temperatures above the standard photocoagulation threshold, are activated but not coagulated, since the heat can dissipate fast enough that no coagulation takes place. This tissue specific photoactivation (or TSP) allows significant treatment without causing full thickness retinal damage and the associated vision loss.
The use of photoactivation in TSP instead of photocoagulation is meant to distinguish between these new subthreshold MIP treatments and the standard photocoagulation treatment. The standard treatment thermally heats the tissue until it starts to denature the protein structures and, hence, is called photocoagulation. This denaturization initiates a healing response, which ameliorates the disease.
The new MIP treatments heat the tissue and initiate some signal carrier cells, which initiate a healing response and this healing response ameliorates the disease being treated without coagulating any of the retinal layers and without the associated vision loss. Hence, activating the healing response without coagulating tissue and thus losing vision is a better treatment method.
Both of these treatments have been developed and are currently being used in many countries with Infrared lasers.
Physicians have not used green lasers for long sub-threshold treatments (like TTT) because of concerns regarding retinal phototoxicity. They have not used green lasers for pulse trains of short pulses, because current green lasers are unable to deliver similar pulse-width trains as those provided by the above referenced NIR laser with short and controlled pulse widths. By way of illustration, current green lasers employ a fast photodetector or photosensor to sense the output power level of the laser cavity. A software control light loop measures laser output on the millisecond time scale, and increases or decreases the requested energy by increasing or decreasing the requested drive current to the pump diode. This allows a relatively stable laser output, within a few percent, over long time periods such as pulses of tens to hundreds or even thousands of milliseconds.
In addition to the software light loop, a hardware light spike safety protection design has been used. This is an analog circuit that can respond to light energy changes in the microsecond regime. This is used to provide safety against a high power light spike, if some failure or current spike occurs. This protects the patient from spikes being delivered through the delivery system.
However, the hardware light loop threshold is generally set at 10 to 20% above the desired energy level, since it is a safety factor. There are numerous types of laser power fluctuations or changes that occur on this short time scale that can be smaller than this threshold or that bounce back and forth between transverse modes of the laser. These mode hops can cause power fluctuations of up to 10 to 20% before the hardware light loop kicks in. The software light loop is not able to respond to these quick changes and only make the fluctuations worse by trying to respond and varying the requested power.
There is a need to provide a system, and its methods of use, that can respond to these quick changes without making the fluctuations worse.